Lynch Syndrome

Causes of Lynch syndrome

Lynch syndrome is caused by inherited mutations in one of several mismatch repair (MMR) genes—most commonly MLH1, MSH2, MSH6, PMS2, or a deletion in the EPCAM gene. These genes are responsible for correcting errors that occur when DNA is copied during cell division.

Risk factors for Lynch syndrome

• Having one or more first-degree relatives diagnosed with colorectal, endometrial, or other Lynch-associated cancers
• Having a family history of cancers that occurred at younger ages (typically before age 50)
• Personal history of multiple Lynch-associated cancers
• Being of Ashkenazi Jewish descent, which may increase the likelihood of carrying certain gene mutations

Symptoms of Lynch syndrome

Lynch syndrome itself doesn’t cause symptoms. However, the cancers associated with it may include:

• Rectal bleeding or changes in bowel habits (colorectal cancer)
• Unusual vaginal bleeding (endometrial or uterine cancer)
• Abdominal or pelvic pain
• Fatigue or unexplained weight loss

Diagnosing Lynch syndrome

Diagnosis typically involves a combination of family history review, genetic counseling, and genetic testing. Tumor testing (such as microsatellite instability (MSI) testing or immunohistochemistry (IHC)) may be done first to assess whether a tumor has features consistent with Lynch syndrome.

Treatment of Lynch syndrome

There’s no cure for Lynch syndrome itself, but its effects can be managed. Treatment focuses on early detection and prevention of cancers, which may include:

• Regular colonoscopies beginning at a younger age
• Risk-reducing surgery (such as hysterectomy) for women with a high risk of gynecologic cancers
• Aspirin therapy, which may lower colorectal cancer risk
• Enhanced screening for other associated cancers, like stomach, ovarian, and urinary tract cancers
• Cancer treatment if a malignancy is found, which may involve surgery, chemotherapy, or immunotherapy depending on the cancer type